Physical conditioning induces distinct alterations in the autonomic regulation of cardiovascular function and in lipid metabolism. The primary objective of this research is to test the hypothesis that alterations in membrane receptors, or the biochemical processes linked to these receptors, are induced by physical exercise and contribute to the mechanism of altered autonomic control of cardiac function and lipid metabolism which result from physical conditioning. Radioligand binding techniques will be used to directly assess the effects of conditioning upon adrenergic and cholinergic receptors in specialized cardiac pacemaker and conduction tissue and in atrial and ventricular working myocardium of experimental animals, upon adrenergic receptors of rat adipocytes, and upon low density lipoprotein receptors of human lymphocytes. In addition, conditioning effects upon biochemical sequelae of receptor binding such as activation of adenylate cyclase, and upon physiologic sequelae of receptor binding such as cardiac chronotropy and inotropy, adipocyte lipolysis, and plasma LDL concentrations will be assessed. Since available physiologic data are controversial and do not distinguish between receptor and non-receptor mechanisms for the metabolic and cardioregulatory alterations induced by physical conditioning, this research should be instrumental in defining the mechanisms of these effects. In addition, the study of the effects of physical conditioning by these methods may well reveal important features of receptor differentiation and regulation, with implications reaching beyond the analysis of conditioning physiology itself.